Hoechst 33342 efflux identifies a subpopulation of cytogenetically normal CD34+CD38− progenitor cells from patients with acute myeloid leukemia

Feuring‐Buske, Michaela; Hogge, Donna E.

doi:10.1182/blood.v97.12.3882

Cited by 104 publications

(75 citation statements)

References 39 publications

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“…These SP cells are resistant to AML therapies that include drugs that are used for treatment of AML patients like anthracyclines [24]. Purified SP cells were shown to have leukemic initiating capacity in NOD/SCID mouse models [24,25] and contained both CD34+ cells and CD34− cells [26,27] which are indeed in part neoplastic [28]. Although this suggest that a small part of the CD34− cells are therapy resistant, it remains to be established whether the SP cells are candidates for the leukemia-initiating cells in so-called CD34− leukemia.…”

Section: Identification Of Leukemic Stem Cellsmentioning

confidence: 99%

Leukemic stem cells: identification and clinical application

2017

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Section: Identification Of Leukemic Stem Cellsmentioning

confidence: 99%

Leukemic stem cells: identification and clinical application

2017

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“…Interestingly it has been reported that the capacity to efflux Hoechst 33342 (SP) identifies a subpopulation of CD34 þ 38À residual normal cells in AML, whereas CD34 þ 38À Hoechst bright cells were leukemic. 62 Although these authors could not relate Hoechst 33342 efflux with ABCB1 protein expression in the overall SP of cells, this was not investigated in the CD34 þ 38À subset. Moreover, recent gene expression studies revealed significantly lower levels of ABCB1 transcripts in CD34 þ 38À cells in AML in comparison to normal bone marrow.…”

Section: Abcb1 and Abcg2 In Drug Resistance Of Aml Cd34 þ 38à Hematopmentioning

confidence: 99%

ATP-binding-cassette transporters in hematopoietic stem cells and their utility as therapeutical targets in acute and chronic myeloid leukemia

Raaijmakers

2007

Leukemia

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ATP-binding-cassette (ABC) transporters are evolutionary extremely well-conserved transmembrane proteins that are highly expressed in hematopoietic stem cells (HSCs). The physiological function in human stem cells is believed to be protection against genetic damage caused by both environmental and naturally occurring xenobiotics. Additionally, ABC transporters have been implicated in the maintenance of quiescence and cell fate decisions of stem cells. These physiological roles suggest a potential role in the pathogenesis and biology of stem cell-derived hematological malignancies such as acute and chronic myeloid leukemia. This paper reviews the (patho)physiological role of ABC transporters in human normal and malignant HSCs and discusses its implications for their utility as therapeutical targets to eradicate leukemic stem cells in these diseases.

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“…Bone marrow-derived SP cells not only demonstrate potent haemopoietic engraftment in mice but also have the potential for plasticity. 4,7,8 SP cells have since been identified in umbilical cord, 9 adult bone marrow 10,11 and adult human peripheral blood. 12 In contrast to observations in murine bone marrow, SP cells from human peripheral blood do not demonstrate a capacity for in vitro culture or engraftment in NOD/SCID mice.…”

Section: Stem Cell Markermentioning

confidence: 99%

Side population/ABCG2-positive cells represent a heterogeneous group of haemopoietic cells: implications for the use of adult stem cells in transplantation and plasticity protocols

Naylor

Jaworska

Branson

et al. 2004

Bone Marrow Transplant

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Summary:Murine side population (SP) cells may have an increased ability to engraft lethally irradiated mice and lack CD34 expression. Strategies using CD34 as a primary marker of haemopoietic stem cells may therefore result in the exclusion of a primitive stem cell population. The molecular basis for the murine SP phenotype has been attributed to the multidrug-resistance transporter ABCG2. This study aimed to investigate ABCG2 expression from a variety of human sources and investigate the relationship between ABCG2 expression, the SP phenotype, and expression of markers such as CD34 and CD133. SP cells were observed in different haemopoietic sources, but a significant increase in the number of SP cells was observed in PB following granulocyte colonystimulating factor mobilisation. No direct correlation between the frequency of SP cells and the expression of ABCG2 was observed. SP cells were identified in both lineage-positive and lineage-negative population and ABCG2 expression was enriched in lineage-negative SP cells. Lineage-negative SP cells were devoid of CD34 expression but enriched for CD133. Subsequent analysis revealed that ABCG2 and CD133 are coexpressed. Together, these data suggest that the ABCG2 transporter is neither required nor responsible for the SP phenotpye in many human blood cells.

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Hoechst 33342 efflux identifies a subpopulation of cytogenetically normal CD34+CD38− progenitor cells from patients with acute myeloid leukemia

Cited by 104 publications

References 39 publications

Leukemic stem cells: identification and clinical application

Leukemic stem cells: identification and clinical application

ATP-binding-cassette transporters in hematopoietic stem cells and their utility as therapeutical targets in acute and chronic myeloid leukemia

Side population/ABCG2-positive cells represent a heterogeneous group of haemopoietic cells: implications for the use of adult stem cells in transplantation and plasticity protocols

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